The objective of this research is to gain an understanding, on a molecular level, of the pharmacological basis of gamma-aminobutyric acid (GABA) mediated synaptic transmission. Whereas a considerable body of electrophysiological and biochemical information is available for the nicotinic and muscarinic cholinergic receptors, and for the adrenergic receptor, a similar depth of fundamental knowledge of GABA receptor function requires further investigation. A thorough study of the pharmacological basis for the postsynaptic action of GABA in a defined preparation derived from the vertebrate central nervous system will add significantly to our understanding of GABA receptor action. We have previously shown that GABA is used like a neurotransmitter in embryonic chick spinal cord neurons grown in primary monolayer cell culture. Standard intracellular microelectrode recording techniques have been combined with the application of known concentrations of drugs to single neurons by multiple barrel pressure pipets, permitting the determination of complete dose response curves for transmitters and modulators on individual neurons. The GABA induced conductance of such neurons is potentiated by benzodiazepine tranquilizers and inhibited by certain anxiety producing beta-carbolines. The principal goal of this proposal is to investigate the mechanism of positive and negative control of GABA induced conductance increases. A study of the effects of GABA agonists and antagonists, and modulators of GABA action on the kinetics of desensitization will be carried out.